Joanne Trinh

Joanne Trinh
Universität zu Lübeck

PhD

About

71
Publications
11,096
Reads
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2,091
Citations
Citations since 2016
49 Research Items
1697 Citations
20162017201820192020202120220100200300
20162017201820192020202120220100200300
20162017201820192020202120220100200300
20162017201820192020202120220100200300
Additional affiliations
March 2017 - present
Universität zu Lübeck
Position
  • Group Leader
September 2012 - November 2016
University of British Columbia - Vancouver
Position
  • PhD Student

Publications

Publications (71)
Article
Background: Leucine-rich repeat kinase 2 (LRRK2) mutation 6055G→A (Gly2019Ser) accounts for roughly 1% of patients with Parkinson's disease in white populations, 13-30% in Ashkenazi Jewish populations, and 30-40% in North African Arab-Berber populations, although age of onset is variable. Some carriers have early-onset parkinsonism, whereas others...
Article
While many genetic causes of movement disorders have been identified, modifiers of disease expression are largely unknown. X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease caused by a SINE-VNTR-Alu(AGAGGG)n retrotransposon insertion in TAF1, with an expanded (AGAGGG)n. Repeat length and variants in MSH3 and PMS2, explain ∼65% of...
Preprint
Biallelic mutations in PINK1 and PRKN cause recessively inherited Parkinson’s disease (PD). Though some studies suggest that PINK1 / PRKN monoallelic mutations may not contribute to risk, deep phenotyping assessment showed that PINK1 or PRKN monoallelic pathogenic variants were at a significantly higher rate in PD compared to controls. Given the es...
Article
Full-text available
Background: Sequencing quality has improved over the last decade for long-reads, allowing for more accurate detection of somatic low-frequency variants. In this study, we used mixtures of mitochondrial samples with different haplogroups (i.e., a specific set of mitochondrial variants) to investigate the applicability of nanopore sequencing for low-...
Article
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Objective The effect of environmental and lifestyle factors on patients with LRRK2 p.Gly2019Ser (LRRK2+/PD+) compared to idiopathic PD (iPD) has yet to be thoroughly investigated. Methods In a homogeneous Tunisian Arab Berber population, we recruited 200 idiopathic PD and 199 LRRK2 p.Gly2019Ser mutation carriers, of whom 142 had PD (LRRK2+/PD+) and...
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Purpose Subclinical alterations of the vaginal microbiome have been described to be associated with female infertility and may serve as predictors for failure of in vitro fertilization treatment. While large prospective studies to delineate the role of microbial composition are warranted, integrating microbiome information into clinical management...
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Background: Coding and noncoding repeat expansions are an important cause of neurodegenerative diseases. Objective: This study determined the clinical and genetic features of a large German family that has been followed for almost 2 decades with an autosomal dominantly inherited spinocerebellar ataxia (SCA) and independent co-occurrence of amyot...
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Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Genetic modifiers, environmental factors and gene–environment interactions have been found to modify PD risk and disease progression. The objective of this study was to evaluate the association of smoking, caffeine and anti-inflammatory drugs with age at onset (AAO) in a large PD...
Article
Mutations in Leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of dominantly inherited Parkinson's disease (PD). LRRK2 mutations, among which p.G2019S is the most frequent, are inherited with reduced penetrance. Interestingly, the disease risk associated with LRRK2 G2019S can vary dramatically depending on the ethnic background of th...
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Background: Mutations in the E3 ubiquitin ligase parkin cause autosomal recessive Parkinson's disease (PD). Together with PTEN-induced kinase 1 (PINK1), parkin regulates the clearance of dysfunctional mitochondria. New mitochondria are generated through an interplay of nuclear- and mitochondrial-encoded proteins, and recent studies suggest that pa...
Article
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X-linked dystonia–parkinsonism (XDP) is a severe neurodegenerative disorder that manifests as adult-onset dystonia combined with parkinsonism. A SINE-VNTR-Alu (SVA) retrotransposon inserted in an intron of the TAF1 gene reduces its expression and alters splicing in XDP patient-derived cells. As a consequence, increased levels of the TAF1 intron ret...
Preprint
Background: While multiple genetic causes of movement disorders have been identified in the past decade, modifying factors of disease expression are still largely unknown for most conditions. X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative disease caused by a SINE-VNTR-Alu (SVA)-type retrotransposon insertion that contains a...
Article
Full-text available
Background: X-linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative disorder characterized by progressive dystonia and parkinsonism. It is caused by a SINE-VNTR-Alu (SVA) retrotransposon insertion in the TAF1 gene with a polymorphic (CCCTCT)n domain that acts as a genetic modifier of disease onset and expressivity. Methods: Here...
Chapter
X-linked dystonia-parkinsonism (XDP) is a neurodegenerative movement disorder endemic to the Philippines. The disease is caused by the antisense insertion of a SINE-VNTR-Alu (SVA)-type retrotransposon within an intron of the TAF1 gene. Within the SVA, there is a polymorphic hexanucleotide repeat domain, (CCCTCT)n, which varies between 30 and 55 rep...
Preprint
Full-text available
Parkinson's disease (PD) is a progressive neurodegenerative disorder. Genetic modifiers, environmental factors and gene-environment interactions have been found to modify PD risk and disease progression. The objective of this study was to evaluate the association of smoking, caffeine and anti-inflammatory drugs with age at onset (AAO) and clinical...
Article
Full-text available
Objective: To establish a workflow for mitochondrial DNA (mtDNA) CpG methylation using Nanopore whole-genome sequencing and perform first pilot experiments on affected Parkin biallelic mutation carriers (Parkin-PD) and healthy controls. Background: Mitochondria, including mtDNA, are established key players in Parkinson's disease (PD) pathogenesis....
Article
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Background: Pathogenic variants in the Leucine-rich repeat kinase 2 ( LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2 -linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities a...
Article
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Objective Our study investigated the presence of regional differences in hexanucleotide repeat number in postmortem brain tissues of 2 patients with X-linked dystonia-parkinsonism (XDP), a combined dystonia-parkinsonism syndrome modified by a (CCCTCT) n repeat within the causal SINE-VNTR- Alu retrotransposon insertion in the TAF1 gene. Methods Gen...
Article
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Objective: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. // Methods: We performed the first genomewide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at...
Article
Full-text available
Objective: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. Methods: We performed the first genome-wide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases a...
Article
This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6, FBXO7, SYNJ1, and VPS13C genes. We screened 673 citations and extracted genotypic and phenotypic data for 140 patients (73 families) from 77 publications. In an exploratory fashion, we a...
Preprint
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The level and the biological significance of mitochondrial DNA (mtDNA) methylation in human cells is a controversial topic. Using long-read third-generation sequencing technology, mtDNA methylation can be detected directly from the sequencing data, which overcomes previously suggested biases, introduced by bisulfite treatment-dependent methods. We...
Preprint
Full-text available
Objective: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. Methods: We performed the first genome-wide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at t...
Article
Full-text available
Objective: Even though genetic predisposition has proven to be an important element in Parkinson's disease (PD) etiology, monozygotic (MZ) twins with PD displayed a concordance rate of only about 20% despite their shared identical genetic background. Methods: We recruited five pairs of MZ twins discordant for idiopathic PD and established skin fib...
Article
Full-text available
Several mutations in Leucine-rich repeat kinase-2 (LRRK2) have been associated with Parkinson’s disease (PD). The most common substitution, G2019S, interferes with LRRK2 kinase activity, which is regulated by autophosphorylation. Yet, the penetrance of this gain-of-function mutation is incomplete, and thus far, few factors have been correlated with...
Article
Full-text available
The LRRK2 gene has rare (p.G2019S) and common risk variants for Parkinson’s disease (PD). DNM3 has previously been reported as a genetic modifier of the age at onset in PD patients who carry the LRRK2 p.G2019S mutation. We analysed this effect in a new cohort of LRRK2 p.G2019S heterozygotes (n = 724) and meta-analysed our data with previously publi...
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Neurometabolic disorders are often inherited and complex disorders that result from abnormalities of enzymes important for development and function of the nervous system. Recently, biallelic mutations in NAXE (APOA1BP) were found in patients with an infantile, lethal, neurometabolic disease. Here, exome sequencing was performed in two affected sist...
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We present a case of mild, adult-onset dopa-responsive dystonia (DRD) with a heterozygous mutation in the tyrosine hydroxylase (TH) gene. We propose that this genetic state may have led to partial enzyme deficiency. Future studies should attempt to identify and characterize the phenotype of other patients with single TH variants.
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Background: Although most cases of Parkinson´s disease (PD) are idiopathic with unknown cause, an increasing number of genes and genetic risk factors have been discovered that play a role in PD pathogenesis. Many of the PD-associated proteins are involved in mitochondrial quality control, e.g., PINK1, Parkin, and LRRK2, which were recently identif...
Article
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Introduction: Genome-wide association studies (GWAS) have identified multiple loci associated with Parkinson's disease (PD) risk. The presence of rare variants within these loci that may account for the increased susceptibility requires further investigation.Methods: Using exome sequencing, we performed a comprehensive rare variant screen of genes...
Preprint
Objective To assess genetic modifiers of Parkinson’s disease (PD) age at onset (AAO) penetrance in individuals carrying common and rare LRRK2 risk alleles Methods We analysed reported genetic modifier DNM3 rs2421947 in 724 LRRK2 p.G2019S heterozygotes using linear regression of AAO. We meta-analysed our data with previously published data (n=754)....
Article
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Background: Rare denovo variants represent a significant cause of neurodevelopmental delay and intellectual disability (ID). Methods: Exome sequencing was performed on 4351 patients with global developmental delay, seizures, microcephaly, macrocephaly, motor delay, delayed speech and language development, or ID according to Human Phenotype Ontol...
Article
De novo variants represent a significant cause of neurodevelopmental delay and intellectual disability. A genetic basis can be identified in only half of individuals who have neurodevelopmental disorders (NDDs); this indicates that additional causes need to be elucidated. We compared the frequency of de novo variants in patient-parent trios with (n...
Article
Background: Although the genetic load is high in early-onset Parkinson's disease, thorough investigation of the genetic diagnostic yield has yet to be established. The objectives of this study were to assess variants in known genes for PD and other movement disorders and to find new candidates in 50 patients with early-onset PD. Methods: We searche...
Article
This comprehensive MDSGene review is devoted to the three autosomal‐dominant PD forms: PARK‐SNCA, PARK‐LRRK2, and PARK‐VPS35. It follows MDSGene's standardized data extraction protocol, screened a total of 2,972 citations, and is based on fully curated phenotypic and genotypic data on 937 patients with dominantly inherited PD attributed to 44 diffe...
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Approximately 1–3% of children have intellectual disability or global developmental delay. Heterozygous mutations have emerged as a major cause of different intellectual disability syndromes. In severely affected patients, reproductive fitness is impaired and mutations have usually arisen de novo. Massive parallel sequencing has been an effective m...
Article
Objective: To identify novel causes of recessive ataxias, including spinocerebellar ataxia with saccadic intrusions, spastic ataxias and spastic paraplegia. Methods: In an international collaboration, we independently performed exome sequencing in seven families with recessive ataxia and/or spastic paraplegia. To evaluate the role of VPS13D mutatio...
Article
View Supplementary Video Whole exome, genome sequencing, and other massive parallel next generation sequencing technologies have increasingly been used as a clinical diagnostic tool in recent years. Although sequencing technologies are becoming more affordable and widely used, the interpretation of variants from these large datasets at the level o...
Article
Approximately 2–5% of children are born with congenital abnormalities that manifest into more severe neurodevelopmental problems as they age.¹ Neurodevelopmental disorders encompass a wide range of severity and behavioral differences, many of which arise from de novo mutations in critical genes during early brain development.2, 3 Exome sequencing h...
Article
Background An initial diagnosis of Parkinson's disease (PD) is challenging, especially in patients who have early onset and atypical disease. A genetic etiology for parkinsonism, when established, ends that diagnostic odyssey and may inform prognosis and therapy. The objective of this study was to elucidate the genetic etiology of parkinsonism in p...
Article
http://www.sciencedirect.com/science/article/pii/S1353802015003028
Article
Full-text available
It has been almost two decades since the first genetic form of Parkinson’s disease (PD), a point mutation in the α-synuclein gene (SNCA), was identified.¹ Remarkable technological advancements in recent times have accelerated genetic discovery for PD and nominated potential molecular pathways for therapeutic intervention strategies. To date, pathog...
Article
BackgroundA novel mutation (p.N855S) in DNAJC13 has been linked to familial, late-onset Lewy body parkinsonism in a Dutch-German-Russian Mennonite multi-incident kindred.MethodsDNAJC13 was sequenced in 201 patients with parkinsonism and 194 controls from Canada. Rare (minor allele frequency < 0.01) missense variants identified in patients were geno...
Chapter
LRRK2-related Parkinson disease (PD) is characterized by features consistent with idiopathic PD: initial motor features of slowly progressive asymmetric tremor at rest and/or bradykinesia, cog-wheel muscle rigidity, postural instability, and gait abnormalities including festination and freezing. Non-motor symptoms in LRRK2-related PD occur with the...
Article
A pathogenic mutation (VPS35 p.D620N) within the retromer complex has been shown to segregate with late-onset Parkinson's disease (PD). Several studies have subsequently detected the mutation in patients with PD and not in controls. Mutation screening of the coding regions of the retromer cargo recognition complex genes (VPS26A/B, VPS29, and VPS35)...
Article
Importance Mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13 have been implicated in late-onset familial parkinsonism. However, the estimated disease penetrance of these mutations varies widely.Objective To compare penetrance of various mutations reported in published genetic studies to improve the understanding of late-onset parkinsonism.Data...
Article
Human disease is rarely a matter of all or nothing; variable expressivity is generally observed. Part of this variability is explained by somatic mosaicism, which can arise by a myriad of genetic alterations. These can take place at any stage of development, possibly leading to unusual features visible at birth, but can also occur later in life, co...
Article
In recent years, the molecular etiology of parkinsonism has yielded to genetic analysis.¹ Mutations in the gene leucine-rich repeat kinase 2 (LRRK2) have the highest genotypic and population attributable risk. Disparate penetrance estimates have been reported using a variety of statistical analyses, ethnic populations, and sample sizes.² We compare...
Article
Parkinson disease is a progressive neurodegenerative disease for which leucine-rich repeat kinase 2 (LRRK2 carriers) p.G2019S confers substantial genotypic and population attributable risk. With informed consent, we have recruited clinical data from 778 patients from Tunisia (of which 266 have LRRK2 parkinsonism) and 580 unaffected subjects. Motor,...
Article
Full-text available
A Saskatchewan multi-incident family was clinically characterized with Parkinson disease (PD) and Lewy body pathology. PD segregates as an autosomal dominant trait, which could not be ascribed to any known mutation. DNA from three affected members were subjected to exome sequencing. Genome alignment, variant annotation and comparative analyses were...
Article
Full-text available
Parkinson disease (PD) is a multifactorial neurodegenerative disease that was long considered the result of environmental factors. In the past 15 years, however, a genetic aetiology for PD has begun to emerge. Here, we review results from linkage and next‑generation sequencing studies of familial parkinsonism, as well as candidate gene and genome‑...
Article
Full-text available
Background: Alpha-synuclein plays a central role in the pathophysiology of Parkinson's disease. Three missense mutations in SNCA, the gene encoding alpha-synuclein, as well as genomic multiplications have been identified as causes for autosomal-dominantly inherited Parkinsonism. Methods: Here, we describe a novel missense mutation in exon 4 of S...